The Bioinformatics and Molecular Modeling Research Support Core (BMMC) will offer computational tools, expertise, and services in three areas as follows: (1) Analysis of data obtained by high throughput genomic technologies (microarray and RNA-sequencing experiments), and integration with public data repositories. Three of five research projects of this proposal employ oligonucleotide arrays or high-throughput sequencing (HTS) methods to determine the genomic and epigenomic effects of Superfund chemicals. (2) High-throughput in vitro screening of chemicals, and modeling of the association of their transcriptional responses with adverse phenotypes and with other perturbations. (3) Modeling the interactions between xenobiotics and protein receptors using methods of structural bioinformatics and computational toxicology, including some tools originally developed by the BMMC for structure-based drug design. The analyses will focus on aryl hydrocarbon receptor (AHR) and AHR-interacting protein (AIP) (Project 4) and on nuclear receptors peroxisome proliferator activated receptor ? (PPAR?) and retinoid X receptor (RXR), as well as cytochrome P450 enzymes in fish (Project 5). While the projects generate information on the effects of various chemicals on cells and whole organisms, computational studies of receptor-ligand interactions will help to develop hypotheses on the mechanisms at the molecular level and to design specific binding and activity experiments for validation. The Core will be a full-service bioinformatics and molecular modeling research support center for the statistical analysis and interpretation of genomic data and for the design of receptor-ligand interactions studies, providing the computational infrastructure to deal with large amounts of data and manage a large variety of bioinformatics, statistical, and molecular modeling software tools. The Core Leader has a 16-year long experience in the design and development of computational methods for the analysis and integration of genomic data, and will direct a full-time postdoctoral associate with Bioinformatics training. They will analyze microarray and HTS data, working together with graduate students and post-doctoral fellows from the individual projects, who will gain direct, first-hand training in these techniques and methods through their interaction with the Core. The Core Co-Investigator/Co-Leader is an expert in molecular modeling, and will work with an experienced Research Assistant Professor on modeling interactions between environmental pollutants and protein receptors as required by the BUSRP projects.